It's my pleasure to introduce our next guest from Fractyl Health, Co-founder and CEO, Dr. Harith Rajagopalan. Harith, I know you want to start by providing a presentation, an overview of the company. So why don't you go ahead with that, and then we'll proceed to Q&A. Thanks, Keay. Appreciate it. And thanks to all of you for the invitation to come to Chardan. We are focused on obesity and type 2 diabetes, but our approach is differentiated because our focus is on eradicating disease rather than developing chronic disease management tools. That is a fundamental differentiator for what we are aiming to accomplish in this space. The way that we're doing that is by developing game-changing therapies that target root causes of obesity and type 2 diabetes. One of them is a medical device targeting the duodenum, which is the first portion of the small intestine, which is our Revita system that is in late-stage development in the United States, already approved in Europe, reimbursed in Germany, that addresses a root cause of obesity and type 2 diabetes in the gut, with multiple data readouts starting in the fourth quarter of this year. We expect to enter the clinic in 2025 for Rejuva, a preclinical one-and-done pancreatic gene therapy platform for obesity and diabetes. And the preclinical data that we have generated thus far in head-to-head studies against current best-in-class GLP-1 therapies demonstrates the incredible potential for a one-and-done solution for obesity and diabetes via pancreatic gene therapy. Our management team and board have deep experience both in biotechnology, gene and cell therapy, and in medical devices. And we have cash and cash equivalents of $102 million as of June of this year. Our assets are designed simply to prevent and reverse disease. And in a world with incredible GLP-1 drugs, you might ask, what is the purpose of needing to think about eradicating the disease? But I would argue to you that that is where the unmet need has now shifted. We have powerful GLP-1 drugs and more coming that are different versions of exactly the same thing that already exists, but they have significant limitations. And all of the drugs that are in development in the class have high rates of prescription, but also high rates of discontinuation with attendant rapid rebound of weight gain. We're now in a world where we can help people lose weight, but we can't help them keep it off. And you cannot expect that more than half of the patients with obesity will take chronic medications to try to manage their disease. So the entirety of the chronic drug therapy space is fighting for about half of the patient population, leaves 50 million people in the United States with obesity who cannot be expected to take chronic medicines for the rest of their life to manage their obesity. And that's where we come in. Our endoscopic solutions offer durable weight maintenance after the discontinuation of medicines. That is not a profile that you will be able to find in any other therapy in development to our knowledge. We have weight maintenance data that will start in the fourth quarter of this year, and our pivotal study top-line readout in type 2 diabetes will be in mid-2025. In parallel, the Rejuva pancreatic gene therapy preclinical data suggests the potential remission of metabolic disease, and a candidate has already been nominated for type 2 diabetes. We anticipate nominating a candidate for obesity before the end of this year, and we'll initiate a first-in-human study for type 2 diabetes next year. Obesity is the single biggest healthcare market opportunity, and within that, the single biggest unmet need has now shifted from weight loss to weight maintenance. While many new entrants into the space are chasing competition for comparable weight loss to the existing excellent daily and weekly GLP-1 drugs that already dominate the market, the newer drugs do not solve the biggest problem that remains in the space, which is high discontinuation rates and weight rebound. So much so that the advertising for both Wegovy and Zepbound include disclaimers attesting to the fact that discontinuation will lead to weight regain, and most people who stop taking GLP-1s do not restart another one within one year, so the argument that people are going to bounce on and off of these drugs is actually not substantiated by the evidence in the market thus far. What that means is that most people who start taking these drugs stop taking them, do not start another one, and so they are at risk of weight regain. You can see from Novo and Lilly's own data that within one year after withdrawal, participants lose whatever clinically meaningful weight loss they once would have enjoyed. What's worse is if you look at insurer data from Blue Cross Blue Shield, private insurer survey of 170,000 unique GLP-1 drug users, you'll find that more than 30% discontinue within the first month of use, and less than half of them are still on therapy at 12 weeks. What is the point of an insurer paying for a GLP-1 therapy for obesity if the portion of patients who stay on drug is less than 50% at three-to-six months, and then weight regain is going to occur? The reason that Blue Cross Blue Shield is putting this out, in our view, is because they're describing a major problem that they are facing with demand for reimbursement, but lack of real-world pull-through. So whatever you're seeing in the phase three studies have not been demonstrated to be proving themselves out in the real world because of what's happening on this graph and the graph just before it. So our technologies are designed to be sustained solutions to address the needs of the majority of people who won't be on chronic therapy for the rest of their lives. Revita is a medical device targeting the duodenal mucosa, and it aims to ablate and regenerate a healthy mucosa that resets the gut-brain signals that are important to durably lower the body's metabolic setpoint, something that drugs cannot do. And Rejuva targets the pancreas and aims to capture the powerful mechanism of GLP-1s, but deliver them in a durable manner that does not depend on ongoing medical therapy. And as a consequence, has more likelihood of being able to actually achieve in the real world what the GLP-1 drugs have demonstrated in their phase three studies, but are not demonstrating to date in the real world. I'm going to spend a few minutes talking about Revita here just to lay the context, and then we're going to have a deeper discussion with Keay about the gene therapy program because of the conference that you all are attending. We've developed a piece of capital equipment that enables GI endoscopists to perform a high-volume endoscopic procedure. We have a single-use catheter with Revita that is designed to offer durable and repeatable metabolic improvement. We have a very broad IP estate covering the methods, the systems, and the devices of ablating the duodenal mucosa. And as I mentioned to you earlier, we are reimbursed and initiating marketing in Germany and have Breakthrough Device Designation from the FDA for this device in both weight maintenance in obesity and in insulin-treated type 2 diabetes. In Europe, where Revita is already approved, we've initiated a real-world registry in patients with obesity and type 2 diabetes. And we presented earlier this year the results at one year for the initial tranche of patients who've been going through the registry. And you can see that weight has reduced in this cohort from 111 kg to 97 kg at one year, representing nearly a 13% total body weight loss. Then hemoglobin A1c has improved from 9.6% to low 7s, suggesting a very significant improvement in hemoglobin A1c, albeit from a very high baseline, an abnormally high baseline compared to most clinical studies. Nevertheless, Revita was very well tolerated. Now you imagine the experience of a patient who just has to say that they're not going to eat anything after dinner the night before a procedure, go in for a 40-minute outpatient endoscopic procedural therapy, go back to their daily lives immediately thereafter, and one year later, without being asked to change their lifestyle in any meaningful way, are now experiencing substantial reductions in both weight and in blood sugar without needing to add medicines. That is a profile that we think is going to be very compelling in the market. The Remain-1 pivotal study is underway for weight maintenance in the United States. We have a planned midpoint data analysis anticipated in Q2 of 2025. We have already initiated this study in the third quarter. We're starting patients who are new to GLP-1s, obese non-diabetics, on tirzepatide. We're going to get them to 15% total body weight loss, and once they achieve 15% total body weight loss, we will discontinue the tirzepatide and then randomize them to either undergoing the Revita procedure or a sham procedure, and then following them through 6 and 12 months. The FDA has granted us Breakthrough Device Designation for this indication, which confers a clearer regulatory path if the study is successful, but also confers a clearer reimbursement path with CMS upon PMA approval. We're incredibly excited to be able to test Revita's ability to be able to maintain both body weight loss and all of the attendant other risk factors associated with obesity, cardiovascular risk, blood sugar risk, etc., without asking patients to have to stay on medicines for a long time. We're going to have open label data starting in the fourth quarter of this year from an initial tranche of patients. We'll have randomized midpoint data analysis from the first 45 subjects who've been randomized and followed for 12 weeks in Q2 of next year. We're going to continue to enroll that through a pivotal study. We also have a Revitalize-1 study underway. We also have Breakthrough Device Designation in type 2 diabetes from the FDA. This is a simple study to assess the lowering of hemoglobin A1c in patients with inadequately controlled type 2 diabetes. What we have observed from our clinical trials and from our German registry is that a substantial fraction of patients with high blood sugar do not want to take yet another medicine. That the driver of the decision to undergo Revita is the avoidance of complicating their already complicated pharmaceutical regimen. In particular, avoiding either the initiation of injectable therapy or the initiation of insulin per se. Both of these things are highly unattractive and a reason for patients to choose Revita. Now turning to gene therapy. We have developed a local AAV-delivered pancreatic gene therapy that is designed to improve islet function in a durable manner. AAV can achieve transduction of the pancreatic islets. We already know that intra-islet GLP-1 signaling can restore beta cell health and function in obesity and in diabetes. GLP-1-based pancreatic gene therapy can offer substantially differentiated benefit over the existing drugs in the class, partially because they can offer high local levels of GLP-1 with low systemic exposure, but then also because they can offer meal-regulated delivery of GLP-1 because it's driven by the insulin promoter, something we'll talk about more, I bet, in our Q&A. So far, we have demonstrated robust preclinical proof of concept in relevant preclinical regulatory models in head-to-head studies against semaglutide. On day one, obese mice were randomized to either chronic semaglutide, shown in blue, versus one-time GLP-1 gene therapy, shown in red. So these are mice that either have to get chronic semaglutide or a single dose administration of the GLP-1 gene therapy. On day 29, we withdrew the semaglutide from animals. Then those animals in the blue cohort were then secondarily randomized to either placebo or a single injection of the Rejuva gene therapy candidate. What you can see is that animals that stopped taking the semaglutide, like humans, rapidly regain weight, double their food intake immediately upon semaglutide cessation, become ravenous, and then go right back to the weight that they started with, whereas the animals that get a single dose of the pancreatic gene therapy are able to maintain that weight in a durable manner. We have studies that are ongoing, and the effects so far are lasting as long as we've been able to follow these mice. That suggests that the durability of this therapeutic effect, we think, should be quite long-lasting in humans. As I mentioned, we've nominated Rejuva 001 for type 2 diabetes, a nutrient-responsive GLP-1. The vector is an AAV9 vector. It's a human GLP-1 transgene sequence using the human insulin promoter to restrict the expression to the pancreatic beta cells, and it's delivered by a proprietary endoscopic needle that we have developed, which we think is the key unlock for pancreatic gene therapy, and we can effectively transduce islets with a one-time intrapancreatic administration to get nutrient-responsive GLP-1 expression. We're in IND enablement right now. Expect the clinical study to begin next year, and so our pipeline is designed to end obesity. We have near-term catalysts that will demonstrate the potential to reverse disease, both in obesity and in type 2 diabetes, and both of the assets that we have in development target root causes with a view towards offering sustained solutions for patients living with these diseases, something that drugs that exist or drugs in development are not going to be able to do. Thanks very much. Great. So Harith, I guess my first question is, I know my own career as an analyst. I started out as a medical device analyst, and then I transitioned into covering biotech. And there was a lot of skill and knowledge that I had as a device analyst that carried over. So I wasn't starting from scratch covering biotech. So I guess my question for you is, what is the skill and knowledge that you've acquired developing a medical device? How does that lay a foundation for you to be successful developing a gene therapy? Keay, as I alluded to in the presentation, we think that local delivery is the key enabler for pancreatic gene therapy. You're seeing that in the eye. You see that in the ear. You see that in the brain. No one's really been able to bring gene therapy to the pancreas yet. But we think the reason for that is because no one's figured out a way to access the pancreas safely and reliably. We've developed a proprietary needle catheter that we think can achieve this and has been tested in over 80 Yucatan pigs, which is the appropriate preclinical model for this, demonstrating technical feasibility and safety and reliable dose-dependent delivery. What that allows is a very low dose of gene therapy to be delivered to the pancreas. Since we're using AAV9, which is already approved for Zolgensma, we're looking at two to three orders of magnitude less AAV9 than is already being used for patients with Zolgensma. That lower dose translates also to a lower anticipated COGS, which makes the commercial model imaginable for type 2 diabetes and obesity. Just maybe going back to the science of targeting the islet cells and the expression of GLP-1, how well understood is that process? The beta cells in the pancreas are highly related to the enteroendocrine cells in the gut that generate GLP-1 themselves. They have the same processing enzymes. They have the same ability to package the hormones into vesicles and keep them underneath the membrane surface and then release them on demand. That's how GLP-1 is released in the body in each and every one of us. There are cells in the gut that have made GLP-1. The GLP-1 is sitting there waiting to be released. When you eat a meal that has fat and sugar in it, the enteroendocrine cell senses the sugar. It then releases the GLP-1 into the bloodstream. It binds to local nerves in the gut wall and also enters into the circulation. GLP-1 levels go up and down over the course of the day. We can mimic that with the delivery into the pancreas because the beta cell is all of that same machinery for insulin, which we can leverage to offer very much the same effect. So let's talk about your preclinical data then. And which of it do you think has been most informative in trying to prove your approach and your proof of mechanism and proof of concept? I think that what's really encouraging is that all of the data that we've been generating in preclinical models jives extremely well with what we understand about the GLP-1 mechanism through semaglutide and tirzepatide's development. We've been testing it in the same regulatory models that they have for diabetes in the db/db mouse and then in obesity in the DIO mouse. And in both of those models and head-to-head studies against semaglutide, our gene therapy candidate has outperformed semaglutide on durability and on potency. And obviously, we think convenience because a one-time administration compared to chronic ongoing administration, you have to believe that that's going to deliver a convenience benefit as well. So in both of those models, we've been incredibly heartened by the consistency of the results, the dose dependency of the results. And then we layer on top of that the work that we've done in the large animal models to demonstrate the reliability and feasibility of the delivery at doses that we think are going to be well within the safety envelope of gene therapy. Take those together, that all gives us conviction of the potential success for the candidate. OK. So what might a first-in-human study look like, the design of that study? You may know that in the GLP-1 drug class, there has historically begun with work in type 2 diabetes where efficacy can be achieved at much lower doses than is necessary in obesity. And so if you think about a gene therapy first-in-human study, you're thinking about a single-arm, open-label, dose-escalation trial. You're going to start to see glucose effects before you're going to start to see weight effects. And so we're starting in a type 2 diabetes patient population who also happens to be obese. And there is a very large and very well-understood therapeutic window for the effect that GLP-1 can have in the pancreatic islet before causing any of the tolerability questions associated with systemic administration. Now, we think that we have a better solution to tolerability because our GLP-1 secretion is demand-regulated and much more physiologic than very high pharmacologic doses with sema and tirzepatide. Nevertheless, we're starting in type 2 diabetes, an inadequately controlled patient population who've demonstrated the ability to tolerate GLP-1 drugs at high doses, seen benefit from that. We'll withdraw them from their GLP-1 drug, and then we will administer the gene therapy, and we will be assessing improvements in blood sugar, and then we will be doing dose escalation to then also look at A1c and obesity as well. How are you set up from a manufacturing perspective for your gene therapy drug candidate? Yeah. So we've already announced that we are working with a CDMO named Forge Biologics based in Columbus, Ohio. And they've been fantastic partners. We've done incredible process development improvements already with them, driving down our cost per batch by at least twofold so far and a visibility towards much more improvement than that. Our runs so far have been very high yield and very high quality. AAV9 is in manufacturing. AAV9 is pretty well-understood operations at this point. It's not a novel capsid. It's something that most folks can do, but our partners are excellent at it. Yeah. We're familiar with them. They've presented at our manufacturing summit in the past. OK. Great. That's great. Maybe just go back to the weight loss with the GLP-1s. I think people understand that along with the fat loss, there's kind of this indiscriminate loss of the muscle mass, which is an undesirable side effect. So how might your approach be able to avoid that? Let's take a step back. Any time you lose weight, you're going to lose a combination of fat mass and lean mass. If you and I diet, we're going to lose a combination of fat mass and lean mass as well. Whenever people have assessed the lean mass function in patients with obesity, other than in elderly frail individuals, lean mass function seems to be at least as good, if not improved. I think that this question of lean mass versus fat mass is actually misplaced. The core issue is if people stop taking GLP-1 drugs, they're going to regain fat mass, and they're not going to easily regain lean mass unless they're doing an active exercise regimen. So the risk in the fat mass to lean mass distribution, I think, ties more to discontinuation of the drugs, which is a problem that I think we can help solve rather than in the weight loss to begin with. So maybe just lay out the timeline and the critical path items for Rejuva. So IND enablement is ongoing, filing for a first-in-human study in the first half of 2025. We anticipate beginning to see real data in the second half of 2025. And that'll be the first dose will be designed to be a minimally efficacious dose, which is what the regulators ask for in gene therapy. So something that will achieve enough GLP-1 expression in the islet to be able to impact blood sugar, but in a modest way. That's the goal of a first-in-human first dose in this space. What's worth mentioning is that GLP-1 biology is among the best understood biology in biomedicine today, that the levels of GLP-1 that are achieved and the correlation between those levels and efficacy are very, very well understood. The work that we need to do is to demonstrate our ability to reliably deliver those levels in humans based on the work that we've already been doing in preclinical models. So, you know, your state of what your cash position was, and how far of a runway does that support? We have cash into the fourth quarter of 2025, which gives us an opportunity to get through some of the key milestones that we've just mentioned, both on the Revita program and in the Rejuva program. OK. So, final question. What do you think that investors are missing or really need to understand to fully appreciate your story? I think investors are missing the fact that weight maintenance is the single biggest opportunity in obesity today. Weight maintenance is the key to unlocking the reimbursement in obesity, I think, writ large. And we have two approaches to targeting weight maintenance that are going to be de-risked with key catalysts coming in the next several quarters. And I think that people are just missing because there's so much noise around GLP-1s and next-generation molecules. I think what people are getting enamored by is weight loss and losing sight of the fact that payers are screaming out that these drugs are not delivering results in the real world because of discontinuation. And that's where the problem really resides. OK. Well, very good. We reached the end of our time here, but thank you so much for joining us today. Thank you. Appreciate it. It's my pleasure to. And then we'll proceed to Q&A. Thanks, Keay. Appreciate it. And thanks to all of you for the invitation to come to Chardan. We are focused on obesity and type 2 diabetes, but our approach is differentiated because our focus is on eradicating disease rather than developing chronic disease management tools. That is a fundamental differentiator for what we are aiming to accomplish in this space. The way that we're doing that is by developing game-changing therapies that target root causes of obesity and type 2 diabetes. One of them is a medical device targeting the duodenum, which is the first portion of the small intestine, which is our Revita system that is in late-stage development in the United States, already approved in Europe, reimbursed in Germany, that addresses a root cause of obesity and type 2 diabetes in the gut with multiple data readouts starting in the fourth quarter of this year. We expect to enter the clinic in 2025 for Rejuva, a preclinical one-and-done pancreatic gene therapy platform for obesity and diabetes. And the preclinical data that we have generated thus far in head-to-head studies against current best-in-class GLP-1 therapies demonstrates the incredible potential for a one-and-done solution for obesity and diabetes via pancreatic gene therapy. Our management team and board have deep experience both in biotechnology, gene and cell therapy, and in medical devices. And we have cash and cash equivalents of $102 million as of June of this year. Our assets are designed simply to prevent and reverse disease. And in a world with incredible GLP-1 drugs, you might ask, what is the purpose of needing to think about eradicating the disease? But I would argue to you that that is where the unmet need has now shifted. We have powerful GLP-1 drugs and more coming that are different versions of exactly the same thing that already exists, but they have significant limitations. And all of the drugs that are in development in the class have high rates of prescription, but also high rates of discontinuation with attendant rapid rebound of weight gain. We're now in a world where we can help people lose weight, but we can't help them keep it off. And you cannot expect that more than half of the patients with obesity will take chronic medications to try to manage their disease. So the entirety of the chronic drug therapy space is fighting for about half of the patient population, leaves 50 million people in the United States with obesity who cannot be expected to take chronic medicines for the rest of their life to manage their obesity. And that's where we come in. Our endoscopic solutions offer durable weight maintenance after the discontinuation of medicines. That is not a profile that you will be able to find in any other therapy in development to our knowledge. We have weight maintenance data that will start in the fourth quarter of this year, and our pivotal study top-line readout in type 2 diabetes will be in mid-2025. In parallel, the Rejuva pancreatic gene therapy preclinical data suggests the potential remission of metabolic disease, and a candidate has already been nominated for type 2 diabetes. We anticipate nominating a candidate for obesity before the end of this year, and we'll initiate a first-in-human study for type 2 diabetes next year. Obesity is the single biggest health care market opportunity, and within that, the single biggest unmet need has now shifted from weight loss to weight maintenance. While many new entrants into the space are chasing competition for comparable weight loss to the existing excellent daily and weekly GLP-1 drugs that already dominate the market, the newer drugs do not solve the biggest problem that remains in the space, which is high discontinuation rates and weight rebound, so much so that the advertising for both Wegovy and Zepbound include disclaimers attesting to the fact that discontinuation will lead to weight regain. And most people who stop taking GLP-1s do not restart another one within one year. So the argument that people are going to bounce on and off of these drugs is actually not substantiated by the evidence in the market thus far. What that means is that most people who start taking these drugs stop taking them, do not start another one. And so they are at risk of weight regain. You can see from Novo and Lilly's own data that within one year after withdrawal, participants lose whatever clinically meaningful weight loss they once would have enjoyed. What's worse is if you look at insurer data from Blue Cross Blue Shield, private insurer survey of 170,000 unique GLP-1 drug users, you'll find that more than 30% discontinue within the first month of use, and less than half of them are still on therapy at 12 weeks. What is the point of an insurer paying for a GLP-1 therapy for obesity if the portion of patients who stay on drug is less than 50% at three-to-six months, and then weight regain is going to occur? The reason that Blue Cross Blue Shield is putting this out, in our view, is because they're describing a major problem that they are facing with demand for reimbursement but lack of real-world pull-through. So whatever you're seeing in the phase three studies have not been demonstrated to be proving themselves out in the real world because of what's happening on this graph and the graph just before it. So our technologies are designed to be sustained solutions to address the needs of the majority of people who won't be on chronic therapy for the rest of their lives. Revita is a medical device targeting the duodenal mucosa, and it aims to ablate and regenerate a healthy mucosa that resets the gut-brain signals that are important to durably lower the body's metabolic set point, something that drugs cannot do. Rejuva targets the pancreas and aims to capture the powerful mechanism of GLP-1s but deliver them in a durable manner that does not depend on ongoing medical therapy. As a consequence, has more likelihood of being able to actually achieve in the real world what the GLP-1 drugs have demonstrated in their phase three studies but are not demonstrating to date in the real world. I'm going to spend a few minutes talking about Revita here just to lay the context, and then we're going to have a deeper discussion with Keay about the gene therapy program because of the conference that you all are attending. We've developed a piece of capital equipment that enables GI endoscopists to perform a high-volume endoscopic procedure. We have a single-use catheter with Revita that is designed to offer durable and repeatable metabolic improvement. We have a very broad IP estate covering the methods, the systems, and the devices of ablating the duodenal mucosa, and as I mentioned to you earlier, we are reimbursed and initiating marketing in Germany and have Breakthrough Device Designation from the FDA for this device in both weight maintenance in obesity and in insulin-treated type 2 diabetes. In Europe, where Revita is already approved, we've initiated a real-world registry in patients with obesity and type 2 diabetes, and we presented earlier this year the results at one year for the initial tranche of patients who've been going through the registry, and you can see that weight has reduced in this cohort from 111 kg to 97 kg at one year, representing nearly a 13% total body weight loss. Then hemoglobin A1c has improved from 9.6% to low 7s, suggesting a very significant improvement in hemoglobin A1c, albeit from a very high baseline, an abnormally high baseline compared to most clinical studies. Nevertheless, Revita was very well tolerated. Now you imagine the experience of a patient who just has to say that they're not going to eat anything after dinner the night before a procedure, go in for a 40-minute outpatient endoscopic procedural therapy, go back to their daily lives immediately thereafter, and one year later, without being asked to change their lifestyle in any meaningful way, are now experiencing substantial reductions in both weight and in blood sugar without needing to add medicines. That is a profile that we think is going to be very compelling in the market. The Remain-1 pivotal study is underway for weight maintenance in the United States. We have a planned midpoint data analysis anticipated in Q2 of 2025. We have already initiated this study in the third quarter. We're starting patients who are new to GLP-1s, obese non-diabetics, on tirzepatide. We're going to get them to 15% total body weight loss, and once they achieve 15% total body weight loss, we will discontinue the tirzepatide and then randomize them to either undergoing the Revita procedure or a sham procedure and then following them through 6 and 12 months. The FDA has granted us Breakthrough Device Designation for this indication, which confers a clearer regulatory path if the study is successful, but also confers a clearer reimbursement path with CMS upon PMA approval. And so we're incredibly excited to be able to test Revita's ability to be able to maintain both body weight loss and all of the attendant other risk factors associated with obesity, cardiovascular risk, blood sugar risk, et cetera, without asking patients to have to stay on medicines for a long time. We're going to have open-label data starting in the fourth quarter of this year from an initial tranche of patients. We'll have randomized midpoint data analysis from the first 45 subjects who've been randomized and followed for 12 weeks in Q2 of next year. And we're going to continue to enroll that through a pivotal study. We also have a Revitalize-1 study underway. We also have Breakthrough Device Designation in type 2 diabetes from the FDA. And this is a simple study to assess the lowering of hemoglobin A1c in patients with inadequately controlled type 2 diabetes. What we have observed from our clinical trials and from our German registry is that a substantial fraction of patients with high blood sugar do not want to take yet another medicine. That the driver of the decision to undergo Revita is the avoidance of complicating their already complicated pharmaceutical regimen, and in particular, avoiding either the initiation of injectable therapy or the initiation of insulin per se. Both of these things are highly unattractive and a reason for patients to choose Revita. Now turning to gene therapy, we have developed a local AAV-delivered pancreatic gene therapy that is designed to improve islet function in a durable manner. AAV can achieve transduction of the pancreatic islets. We already know that intra-islet GLP-1 signaling can restore beta cell health and function in obesity and in diabetes. GLP-1-based pancreatic gene therapy can offer substantially differentiated benefit over the existing drugs in the class, partially because they can offer high local levels of GLP-1 with low systemic exposure, but then also because they can offer meal-regulated delivery of GLP-1 because it's driven by the insulin promoter, something we'll talk about more, I bet, in our Q&A. So far, we have demonstrated robust preclinical proof of concept in relevant preclinical regulatory models in head-to-head studies against semaglutide. On day 1, obese mice were randomized to either chronic semaglutide, shown in blue, versus one-time GLP-1 gene therapy, shown in red. So these are mice that either have to get chronic semaglutide or a single dose administration of the GLP-1 gene therapy. On day 29, we withdrew the semaglutide from animals. And then those animals in the blue cohort were then secondarily randomized to either placebo or a single injection of the Rejuva gene therapy candidate. And what you can see is that animals that stop taking the semaglutide, like humans, rapidly regain weight, double their food intake immediately upon semaglutide cessation, become ravenous, and then go right back to the weight that they started with, whereas the animals that get a single dose of the pancreatic gene therapy are able to maintain that weight in a durable manner. We have studies that are ongoing, and the effects so far are lasting as long as we've been able to follow these mice. So that suggests that the durability of this therapeutic effect, we think, should be quite long-lasting in humans. As I mentioned, we've nominated Rejuva 001 for type 2 diabetes, a nutrient-responsive GLP-1. The vector is an AAV9 vector. It's a human GLP-1 transgene sequence using the human insulin promoter to restrict the expression to the pancreatic beta cells. And it's delivered by a proprietary endoscopic needle that we have developed, which we think is the key unlock for pancreatic gene therapy. And we can effectively transduce islets with a one-time intrapancreatic administration to get nutrient-responsive GLP-1 expression. We're in IND enablement right now. Expect the clinical study to begin next year. And so our pipeline is designed to end obesity. We have near-term catalysts that will demonstrate the potential to reverse disease both in obesity and in type 2 diabetes. And both of the assets that we have in development target root causes with a view towards offering sustained solutions for patients living with these diseases, something that drugs that exist or drugs in development are not going to be able to do. Thanks very much. Great. So Harith, I guess my first question is, I know my own career as an analyst. I started out as a medical device analyst, and then I transitioned into covering biotech. And there was a lot of skill and knowledge that I had as a device analyst that carried over. So I wasn't starting from scratch covering biotech. So I guess my question for you is, what is the skill and knowledge that you've acquired developing a medical device? How does that lay a foundation for you to be successful developing a gene therapy? Keay, as I alluded to in the presentation, we think that local delivery is the key enabler for pancreatic gene therapy. You're seeing that in the eye. You see that in the ear. You see that in the brain. No one's really been able to bring gene therapy to the pancreas yet. But we think the reason for that is because no one's figured out a way to access the pancreas safely and reliably. We've developed a proprietary needle catheter that we think can achieve this and has been tested in over 80 Yucatan pigs, which is the appropriate preclinical model for this, demonstrating technical feasibility and safety and reliable dose-dependent delivery. What that allows is a very low dose of gene therapy to be delivered to the pancreas. And since we're using AAV9, which is already approved for Zolgensma, we're looking at two to three orders of magnitude less AAV9 than is already being used for patients with Zolgensma. And that lower dose translates also to a lower anticipated COGS, which makes the commercial model imaginable for type 2 diabetes and obesity. Just maybe going back to the science of targeting the islet cells and the expression of GLP-1, how well understood is that process? The beta cells in the pancreas are highly related to the enteroendocrine cells in the gut that generate GLP-1 themselves. They have the same processing enzymes. They have the same ability to package the hormones into vesicles and keep them underneath the membrane surface and then release them on demand. That's how GLP-1 is released in the body in each and every one of us. There are cells in the gut that have made GLP-1. The GLP-1 is sitting there waiting to be released. When you eat a meal that has fat and sugar in it, the enteroendocrine cell senses the sugar. It then releases the GLP-1 into the bloodstream. It binds to local nerves in the gut wall and also enters into the circulation. GLP-1 levels go up and down over the course of the day. We can mimic that with the delivery into the pancreas because the beta cell is all of that same machinery for insulin, which we can leverage to offer very much the same effect. So let's talk about your preclinical data then. And which of it do you think has been most informative in trying to prove your approach and your proof of mechanism and proof of concept? I think that what's really encouraging is that all of the data that we've been generating in preclinical models jives extremely well with what we understand about the GLP-1 mechanism through semaglutide and tirzepatide's development. We've been testing it in the same regulatory models that they have for diabetes in the db/db mouse and then in obesity in the DIO mouse. And in both of those models and head-to-head studies against semaglutide, our gene therapy candidate has outperformed semaglutide on durability and on potency. And obviously, we think convenience because a one-time administration compared to chronic ongoing administration, you have to believe that that's going to deliver a convenience benefit as well. So in both of those models, we've been incredibly heartened by the consistency of the results, the dose dependency of the results. And then we layer on top of that the work that we've done in the large animal models to demonstrate the reliability and feasibility of the delivery at doses that we think are going to be well within the safety envelope of gene therapy. Take those together, that all gives us conviction of the potential success for the candidate. OK. So what might a first-in-human study look like, the design of that study? You may know that in the GLP-1 drug class, there has historically begun with work in type 2 diabetes where efficacy can be achieved at much lower doses than is necessary in obesity, and so if you think about a gene therapy first-in-human study, you're thinking about a single-arm, open-label, dose-escalation trial. You're going to start to see glucose effects before you're going to start to see weight effects, and so we're starting in a type 2 diabetes patient population who also happens to be obese, and there is a very large and very well-understood therapeutic window for the effect that GLP-1 can have in the pancreatic islet before causing any of the tolerability questions associated with systemic administration. Now, we think that we have a better solution to tolerability because our GLP-1 secretion is demand-regulated and much more physiologic than very high pharmacologic doses with semaglutide and tirzepatide. Nevertheless, we're starting in type 2 diabetes in inadequately controlled patient population who've demonstrated the ability to tolerate GLP-1 drugs at high doses, seen benefit from that. We'll withdraw them from their GLP-1 drug, and then we will administer the gene therapy. We will be assessing improvements in blood sugar. We will be doing dose escalation to then also look at A1c and at obesity as well. How are you set up from a manufacturing perspective for your gene therapy drug candidate? Yeah. So we've already announced that we are working with a CDMO named Forge Biologics based in Columbus, Ohio. And they've been fantastic partners. We've done incredible process development improvements already with them, driving down our cost per batch by at least twofold so far and a visibility towards much more improvement than that. Our runs so far have been very high yield and very high quality. AAV9 is in manufacturing. AAV9 is pretty well-understood operations at this point. It's not a novel capsid. It's something that most folks can do, but our partners are excellent at it. Yeah. We're familiar with them. They've presented at our manufacturing summit in the past. OK. Great. That's great. Maybe just go back to the weight loss with the GLP-1s. I think people understand that along with the fat loss, there's kind of this indiscriminate loss of the muscle mass, which is an undesirable side effect. So how might your approach be able to avoid that? Let's take a step back. Any time you lose weight, you're going to lose a combination of fat mass and lean mass. If you and I diet, we're going to lose a combination of fat mass and lean mass as well. Whenever people have assessed the lean mass function in patients with obesity, other than in elderly frail individuals, lean mass function seems to be at least as good, if not improved. I think that this question of lean mass versus fat mass is actually misplaced. The core issue is if people stop taking GLP-1 drugs, they're going to regain fat mass, and they're not going to easily regain lean mass unless they're doing an active exercise regimen. So the risk in the fat mass to lean mass distribution, I think, ties more to discontinuation of the drugs, which is a problem that I think we can help solve rather than in the weight loss to begin with. So maybe just lay out the timeline and the critical path items for Rejuva. IND enablement is ongoing. Filing for a first-in-human study in the first half of 2025. We anticipate beginning to see real data in the second half of 2025. And that'll be the first dose will be designed to be a minimally efficacious dose, which is what the regulators ask for in gene therapy. So something that will achieve enough GLP-1 expression in the islet to be able to impact blood sugar, but in a modest way. That's the goal of a first-in-human first dose in this space. What's worth mentioning is that GLP-1 biology is among the best understood biology in biomedicine today, that the levels of GLP-1 that are achieved and the correlation between those levels and efficacy are very, very well understood. The work that we need to do is to demonstrate our ability to reliably deliver those levels in humans based on the work that we've already been doing in preclinical models. So, you know, your state of what your cash position was, and how far of a runway does that support? We have cash into the fourth quarter of 2025, which gives us an opportunity to get through some of the key milestones that we've just mentioned, both on the Revita program and in the Rejuva program. OK. So, final question. What do you think that investors are missing or really need to understand to fully appreciate your story? I think investors are missing the fact that weight maintenance is the single biggest opportunity in obesity today. Weight maintenance is the key to unlocking the reimbursement in obesity, I think, writ large, and we have two approaches to targeting weight maintenance that are going to be de-risked with key catalysts coming in the next several quarters, and I think that people are just missing because there's so much noise around GLP-1s and next-generation molecules. I think what people are getting enamored by is weight loss and losing sight of the fact that payers are screaming out that these drugs are not delivering results in the real world because of discontinuation, and that's where the problem really resides. OK. Very good. We've reached the end of our time here, but thank you so much for joining us today. Thank you. Appreciate it.